Experimental induction of epithelial-mesenchymal interconversions.

Under some in vitro conditions, such as exposure to collagen, growth factors and related molecules, and agents affecting DNA methylation, a cell phenotype shift can be observed from an epithelial to a mesenchymal state of differentiation. The reverse process, a mesenchymal-to-epithelial conversion can likewise be obtained by certain experimental manipulations. In some instances the change is fully reversible by removing the inducer substances, but in others the conversion appears to be stable and irreversible. Only a partial modulation of the cell phenotype is often seen, but sometimes a complete switch to a new phenotype occurs, and morphological, biochemical and functional characteristics of the parent cells can be abrogated. In some in vivo models development of sarcomatous tumours can be seen in animals transplanted with several types of carcinoma, and it is possible that in some of these experiments an epithelial-to-mesenchymal conversion has occurred too. In normal embryonic development as well as in pathological lesions including tissue repair, tumour invasion, and some malignant biphasic tumours, changes similar to the ones observed in experimental epithelial-mesenchymal interconversion seem to take place. Therefore, it is conceivable that experimentally-induced phenotype conversions reflect an inherent potential of cells, and that under some experimental circumstances normally silent genetic programs for epithelial or mesenchymal differentiation are activated, thus recapitulating a phenomenon that occurs in physiopathological circumstances in vivo.